E. John Wherry PhD: Professor and Chair, Department of Systems Pharmacology and Translational Therapeutics, Director Institute for Immunology, UPENN
Mark Painter PhD: Postdoctoral fellow, Wherrylab. Expertise in human T cell biology and SARS-CoV-2 vaccine responses
Allie Greenplate PhD: Adjunct Assistant Professor, Department of Systems Pharmacology and Translational Therapeutics, Director Immune Health Platform, UPENN
Nuala Meyer MD, MS: Associate Professor of Medicine, Division of Critical Care, UPENN
Ben Abramoff MD, MS: Assistant Professor of Clinical Physical Medicine and Rehabilitation and Director of the Post-COVID Assessment and Recovery Clinic, UPENN
Michael Harhay PhD, MPH: Assistant Professor of Epidemiology and Medicine, UPENN
This project will determine if CD8 T cells specific for SARS-CoV-2 proteins can be used as blood-based biosensors of SARS-CoV-2 persistence in individuals with Long COVID. The project team will use advanced methods including high resolution profiling of SARS-CoV-2 specific CD8 T cell populations in Long COVID individuals versus controls to identify differences in numbers and/or activation state that might indicate evidence of SARS-CoV-2 persistence. They will additionally employ transcriptional profiling to interrogate T cell perception of viral persistence in Long COVID. This will be achieved by isolating SARS-CoV-2 specific CD8 T cells and performing advanced sequencing to define changes that might occur in Long COVID patients.
A central area of Long COVID research centers on determining if patients with the condition continue to harbor the SARS-CoV-2 virus in a persistent “reservoir” after acute infection. The adaptive immune response can be used as a sensitive detector of viral persistence because, with transcription-based technologies, scientists can elucidate the specific stage of a T cell’s lifespan, including the very recent detection of a specific antigen (such as that created by SARS-CoV-2). It follows that T cell activity and status can be measured to infer the presence of a viral reservoir in Long COVID individuals.
The project team members have decades of experience in the study of T cell activity in chronic viral infection. They have recently taken advantage of these properties of T cells to interrogate T cell activity in several different settings of human biology including using T cells as sensitive probes of influenza vaccine responses, to predict adverse events in cancer immunotherapy, and as biosensors of aging. They will now exploit this concept to investigate if T cell responses (including in response to specific SARS-CoV-2 antigens) can be measured in Long COVID individuals to serve as biosensors of SARS-CoV-2 persistence. The results should provide new insights into persisting viruses as a potential mechanism of Long COVID and would support (or potentially refute) future approaches such as antiviral therapy and/or therapeutic vaccination in Long COVID.